Levings Application 1 Flashcards

1
Q

MHC protein numbers (2)

A
  • humans have 6 different genes encoding MHC proteins, with 2 copies of each gene
  • total of 12 copies
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2
Q

MHC class I (2)

A
  • 3 MHC class I proteins
  • HLA-A, HLA-B, and HLA-C
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3
Q

HLA

A
  • human leukocyte antigen
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4
Q

MHC class II (2)

A
  • 3 MHC class II proteins
  • HLA-DP, HLA-DQ, HLA-DR
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5
Q

how are MHC proteins key for diversity (3)

A
  • many different alleles for each MHC gene
  • polymorphism maximizes probability of binding to peptides from pathogens
  • particular combination of 12 HLAs we each express defines our tissue type
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6
Q

MHC diversity and transplantation

A
  • MHC diversity is why transplanted cells/organs are recognized as non-self
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7
Q

what is the mouse version of the human HLA complex

A
  • mouse H-2 complex
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8
Q

allorecognition

A
  • the ability of an individual organism to distinguish its own tissues from those of another
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9
Q

allorecognition pathways (3)

A
  • direct pathway
  • indirect pathway
  • semidirect pathway
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10
Q

what percentage of recipient T cells participate in direct pathway allorecognition

A
  • 1-7% of T cells participate in direct recognition for any given donor/host pair depending on degree of donor mismatch
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11
Q

allorecognition: direct pathway

A
  • donor APC presents MHC-donor antigen complex to the TCR of a recipient T cell
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12
Q

allorecognition: direct presentation steps (2)

A
  • donor-derived DCs leave the graft, migrate to LNs, and stimulate naive alloantigen-specific T cells
  • activated T cells traffic to graft where they can be restimulated by donor cells expressing MHC and initiate an immune response
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13
Q

which form of presentation is important in early allograft responses

A
  • direct pathway
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14
Q

allorecognition: indirection pathway

A
  • transplanted antigens are processed and presented on recipient MHC from recipient APC to a recipient T cell
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15
Q

allorecognition: semidirect pathway

A
  • transplanted MHC-donor antigen are presented by a recipient APC to a recipient T cells
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16
Q

direct allorecognition types (2)

A
  • peptide centric: donor peptide of donor peptide-MHC is recognized
  • MHC centric: MHC peptide of donor peptide-MHC is recognized
17
Q

transplants vs normal immune response

A
  • capacity of donor-derived cells to participate
  • direct recognition of alloantigens
  • high freq. of alloAg specific cells in both naive and memory T cell pool
  • lifelong presence of Ag
18
Q

infection in transplantation: 1-12 months after transplant (2)

A
  • maximum immune suppression due to immunosuppressants
  • opportunistic infections, relapses, and reactivations
19
Q

infection in transplantation: over 12 months (2)

A
  • late-onset infections
  • opportunistic infections and community-acquired infections
20
Q

clinical application of strategies to induce tolerance (2)

A
  • central tolerance strategies (deletion)
  • peripheral tolerance strategies (anergy & suppression)
21
Q

clinical application of strategies to induce tolerance: central tolerance

A
  • HSC transplantation to re-set central tolerance
22
Q

clinical application of strategies to induce tolerance: peripheral tolerance (2)

A
  • co-stimulation blockade/modulation
  • cell therapy with regulatory immune cells
  • in vivo boosting of regulatory immune cells
23
Q

HSC transplantation: autologous transplantation
- benefit
- risks (2)

A
  • benefit: no risk of graft versus host disease
  • risk: incomplete ablation of autoreactive cells
  • risk: same genetic risk factors in immune cells
24
Q

HSC transplantation: allogeneic transplantation
- benefits (2)
- risk

A
  • benefit: reduced genetic risk of autoimmunity
  • benefit: assuming complete reconstitution, no space for autoreactive cells
  • risk: graft versus host disease
25
Q

allogeneic

A
  • individuals of the same species who are genetically different and immunologically incompatible
26
Q

autologous

A
  • cell/tissues obtained from same individual
27
Q

graft versus host disease

A
  • T cells of the donated stem cells/bone marrow cells attack the host cells
28
Q

Tregs as cellular therapy to induce transplantation tolerance: Treg sources (2)

A
  • can be taken from patient
  • can be from third source (blood donation, cord blood, thymus, etc)
29
Q

Tregs as cellular therapy to induce transplantation tolerance (3)

A
  • Tregs taken from sources and undergo in vitro expansion
  • cell therapy to insert Tregs back into patient
  • Tregs police immune system, regulate and control immune responses to stop graft rejection and graft vs host disease
30
Q

Treg cell therapies examples (7)

A
  • type 1 & 2 diabetes
  • MS
  • rhematoid arthritis
  • IBD
  • allergies
  • allograft rejection
  • graft versus host disease
31
Q

strategies to block Tregs applications (3)

A
  • cancer
  • chronic infections
  • vaccination
32
Q

regulatory cell therapy paper: kidney rejection outcomes

A
  • CTG had slightly lower rate of biopsy confirmed acute rejection compared to RGT
33
Q

regulatory cell therapy paper: infection outcomes

A
  • CTG had lower rate of infection compared to RGT
34
Q

regulatory cell therapy paper: effects on immune cell populations

A
  • RGT patients had major alterations in absolute and relative blood immune cell population composition compared with healthy controls
35
Q

regulatory cell therapy paper: effects on Tregs

A
  • no significant difference in number/proportions of Tregs between groups 60 weeks post-kidney transplant
36
Q

resetting central tolerance: HSCT for solid organ transplant steps (7)

A
  1. conditioning drug regime
  2. transplantation of donor BM
  3. donor HSC engraftment
  4. multilineage chimerism
  5. peripheral tolerance (intragraft)
  6. peripheral tolerance (secondary lymphoid organs)
  7. central tolerance
37
Q

re-setting central tolerance: HSCT for solid organ transplant; thymus (4)

A
  • recipient and donor bone marrow enter thymus
  • alloreactive T cell from both donor and recipient in thymus
  • alloreactive recipient and donor T cells negatively selected and die
  • mature, non-alloreactive T cells escape to blood as a mixed chimera